HDAC3 positively regulates HE4 expression to promote ovarian carcinoma progression
HDAC3 positively regulates HE4 expression to promote ovarian carcinoma progression
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HDAC3正向调节HE4表达促进卵巢癌进展
DOI：
10.1016/j.abb.2019.07.009
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发表时间：
2019-10-30
影响因子：
3.9
通讯作者：
Zhang, Zhenyu
中科院分区：
文献类型：
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作者：
Lou, Tong;Zhuang, Huiyu;Zhang, Zhenyu
目的：探讨组蛋白脱乙酰酶3(HDAC3)和人附睾蛋白4(HE4)在卵巢癌细胞恶性行为中的作用及其相互关系。方法：采用免疫组织化学、Western印迹和实时定量聚合酶链式反应(Real-time PCR)检测HDAC3在卵巢癌细胞中的表达。用创伤愈合实验、Transwell实验和CCK8增殖实验检测转染和HDAC3蛋白处理前后卵巢癌细胞的增殖、侵袭和转移能力。用免疫组织化学方法检测卵巢上皮组织中HDAC3和HE4蛋白的表达水平，并探讨二者之间的关系。结果：HE4是一种HDAC3结合蛋白。HDAC3通过增加HE4的表达促进卵巢癌细胞的增殖、侵袭和迁移。恶性上皮性卵巢组织中HE4和HDAC3的表达水平显著高于良性和正常上皮性卵巢组织。HDAC3基因干扰下调了PI3K/AKT信号通路相关分子P-PI3K/PI3K和P-AKT/AKT的表达。结论：HDAC3在卵巢癌中表达升高，促进卵巢癌细胞的增殖、侵袭和迁移。HDAC3和HE4结合激活PI3K/AKT信号通路，促进卵巢癌的发生，促进卵巢癌细胞的增殖、侵袭和迁移。因此，抑制HDAC3和HE4之间的关系可能对卵巢癌患者具有潜在的治疗价值。
Objective: To identify the relationship between Histone deacetylase 3 (HDAC3) and Human epididymis protein 4 (HE4) and to explore the mechanisms underlying their effects on the malignant behaviors of ovarian carcinoma cells.Methods: The expression levels of HDAC3 in ovarian carcinoma tissues were identified by immunohistochemistry, Western blot and real-time PCR. A wound healing assay, a Transwell assay and a CCK8 proliferation assay were used to assess the proliferation, invasion and metastatic capacities of ovarian carcinoma cells before and after transfection and HDAC3 protein treatment. HDAC3 and HE4 protein expression level in epithelial ovarian tissues were detected by immunohistochemistry, and the relationship between them was examined.Results: HE4 was identified as an HDAC3-interacting protein. HDAC3 promotes ovarian carcinoma cell proliferation, invasion and migration by increasing the expression of HE4. HE4 and HDAC3 expression levels were significantly higher in malignant epithelial ovarian tissues than they were in benign and normal epithelial ovarian tissues. HDAC3 gene interference downregulated the expression of the PI3K/AKT signaling pathway-associated molecules P-PI3K/PI3K and P-AKT/AKT.Conclusion: HDAC3 expression is higher in ovarian carcinoma and promotes ovarian carcinoma cell proliferation, invasion and migration. HDAC3 and HE4 binding activates the PI3K/AKT signaling pathway, enhances ovarian carcinoma and promotes ovarian carcinoma cell proliferation, invasion and migration. Therefore, inhibiting the relationship between HDAC3 and HE4 may therefore have potential therapeutic value in patients with ovarian carcinoma.